Lipid-DNA Nanoparticles as Drug-Delivery Vehicles for the Treatment of Retinal Diseases

被引:5
作者
Schnichels, Sven [1 ]
Simmang, David [1 ]
Loescher, Marina [1 ]
Herrmann, Andreas [2 ,3 ]
de Vries, Jan Willem [1 ]
Spitzer, Martin S. [4 ]
Hurst, Jose [1 ]
机构
[1] Univ Eye Hosp Tubingen, Ctr Ophthalmol, D-72076 Tubingen, Germany
[2] DWI Leibniz Inst Interact Mat, Forckenbeckstr 50, D-52056 Aachen, Germany
[3] Rhein Westfal TH Aachen, Inst Tech & Macromol Chem, Worringerweg 2, D-52074 Aachen, Germany
[4] Univ Eye Hosp Hamburg Eppendorf, Martinistr 52, D-20251 Hamburg, Germany
关键词
retina; drug-delivery; lipid-DNA nanoparticles; fluorophotometry; biodegradable; intravitreal injection; age-related macular degeneration; diabetic retinopathy; eye; DESIGN;
D O I
10.3390/pharmaceutics15020532
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies.
引用
收藏
页数:18
相关论文
共 21 条
[1]   Tunable Hydrophobicity in DNA Micelles: Design, Synthesis, and Characterization of a New Family of DNA Amphiphiles [J].
Anaya, Milena ;
Kwak, Minseok ;
Musser, Andrew J. ;
Muellen, Klaus ;
Herrmann, Andreas .
CHEMISTRY-A EUROPEAN JOURNAL, 2010, 16 (43) :12852-12859
[2]   Intravitreal administration of antisense oligonucleotides: Potential of liposomal delivery [J].
Bochot, A ;
Couvreur, P ;
Fattal, E .
PROGRESS IN RETINAL AND EYE RESEARCH, 2000, 19 (02) :131-147
[3]   Liposomes for intravitreal drug delivery: A state of the art [J].
Bochot, Amelie ;
Fattal, Elias .
JOURNAL OF CONTROLLED RELEASE, 2012, 161 (02) :628-634
[4]   Investigating Ex Vivo Animal Models to Test the Performance of Intravitreal Liposomal Drug Delivery Systems [J].
Christensen, Gustav ;
Barut, Leon ;
Urimi, Dileep ;
Schipper, Nicolaas ;
Paquet-Durand, Francois .
PHARMACEUTICS, 2021, 13 (07)
[5]   DNA nanoparticles for ophthalmic drug delivery [J].
de Vries, Jan Willem ;
Schnichels, Sven ;
Hurst, Jose ;
Strudel, Lisa ;
Gruszka, Agnieszka ;
Kwak, Minseok ;
Bartz-Schmidt, Karl-U. ;
Spitzer, Martin S. ;
Herrmann, Andreas .
BIOMATERIALS, 2018, 157 :98-106
[6]   Recent Perspectives in Ocular Drug Delivery [J].
Gaudana, Ripal ;
Jwala, J. ;
Boddu, Sai H. S. ;
Mitra, Ashim K. .
PHARMACEUTICAL RESEARCH, 2009, 26 (05) :1197-1216
[7]   Pharmacokinetics of Pullulan-Dexamethasone Conjugates in Retinal Drug Delivery [J].
Kickova, Eva ;
Sadeghi, Amir ;
Puranen, Jooseppi ;
Tavakoli, Shirin ;
Sen, Merve ;
Ranta, Veli-Pekka ;
Arango-Gonzalez, Blanca ;
Bolz, Sylvia ;
Ueffing, Marius ;
Salmaso, Stefano ;
Caliceti, Paolo ;
Toropainen, Elisa ;
Ruponen, Marika ;
Urtti, Arto .
PHARMACEUTICS, 2022, 14 (01)
[8]   Toxicology of engineered nanomaterials: Focus on biocompatibility, biodistribution and biodegradation [J].
Kunzmann, Andrea ;
Andersson, Britta ;
Thurnherr, Tina ;
Krug, Harald ;
Scheynius, Annika ;
Fadeel, Bengt .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2011, 1810 (03) :361-373
[9]   Nanoparticles as drug delivery systems in ophthalmology [J].
Loescher, M. ;
Hurst, J. ;
Strudel, L. ;
Spitzer, M. S. ;
Schnichels, S. .
OPHTHALMOLOGE, 2018, 115 (03) :184-189
[10]   Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity [J].
Marano, RJ ;
Toth, I ;
Wimmer, N ;
Brankov, M ;
Rakoczy, PE .
GENE THERAPY, 2005, 12 (21) :1544-1550